CN1132195A - Technique for prodn. of fish oil polyene fatty acid ethylester - Google Patents
Technique for prodn. of fish oil polyene fatty acid ethylester Download PDFInfo
- Publication number
- CN1132195A CN1132195A CN 95118369 CN95118369A CN1132195A CN 1132195 A CN1132195 A CN 1132195A CN 95118369 CN95118369 CN 95118369 CN 95118369 A CN95118369 A CN 95118369A CN 1132195 A CN1132195 A CN 1132195A
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- China
- Prior art keywords
- oil
- fatty acid
- sodium hydroxide
- ethanol
- adds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 235000014113 dietary fatty acids Nutrition 0.000 title claims abstract description 18
- 229930195729 fatty acid Natural products 0.000 title claims abstract description 18
- 239000000194 fatty acid Substances 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 title claims abstract description 15
- 235000021323 fish oil Nutrition 0.000 title claims abstract description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 40
- 235000019198 oils Nutrition 0.000 claims abstract description 31
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000004202 carbamide Substances 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 11
- 238000003756 stirring Methods 0.000 claims abstract description 8
- 239000003921 oil Substances 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 229960004756 ethanol Drugs 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 11
- 238000010792 warming Methods 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 7
- 239000000047 product Substances 0.000 claims description 6
- 239000002826 coolant Substances 0.000 claims description 5
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 5
- 230000018044 dehydration Effects 0.000 claims description 5
- 238000006297 dehydration reaction Methods 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- 210000002700 urine Anatomy 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims description 2
- 239000008157 edible vegetable oil Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 238000002203 pretreatment Methods 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 abstract description 4
- -1 polyene fatty acid Chemical class 0.000 abstract description 4
- 239000011248 coating agent Substances 0.000 abstract 1
- 238000000576 coating method Methods 0.000 abstract 1
- 238000005516 engineering process Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- OVYTZAASVAZITK-UHFFFAOYSA-M sodium;ethanol;hydroxide Chemical compound [OH-].[Na+].CCO OVYTZAASVAZITK-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- TYLNXKAVUJJPMU-UHFFFAOYSA-N ethyl docosa-2,4,6,8,10,12-hexaenoate Chemical compound CCCCCCCCCC=CC=CC=CC=CC=CC=CC(=O)OCC TYLNXKAVUJJPMU-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A process for producing ethyl ester of polyene fatty acid with fish oil inludes such steps as pretreating raw fish oil, lactidization to obtain esterified oil (that is, stirring raw oil in three-necked flask while adding alcohol solution of sodium hydroxide to it for reaction at 40-60 deg.C for 2-6 hr.), coating urea and rectification, characterized by that greatly shortened productive period, low cost and high output and yield rate.
Description
The present invention relates to a kind of new process of production of fish oil polyene fatty acid ethylester, promptly the new process of production of EPA-EE (EPA-E) and docosahexenoic acid ethyl ester (PHA-E) belongs to the pharmaceutical technology field.
Polyene fatty acid and ester compound thereof medically being proved to be the medicine that a class has strong pharmacological action, are mainly used to prevent and treat cardiovascular disorder clinically, welcome by the patient.In prior art, the preparation polyene fatty acid ethylester is that the technical process of EPA-E and PHA-E is: crude fish oil → saponification → freezing press filtration → acidifying → washing → esterification →
The shortcoming of urine bag → refining → former technical process of fish oil polyene fatty acid ethylester (EPA-E and DHA-E): the one, technical process is oversize, and the 2nd, solvent-oil ratio is big, and the 3rd, product yield is lower.
The objective of the invention is to improve the production technique of original fish oil polyene fatty acid ethylester, adopt the lactide reaction,, shorten the production cycle of former technology greatly to replace saponification, acidifying and the esterification in the former technology, with reduction raw materials consumption and production cost, and improve output and productive rate.
The new process of production of fish oil polyene fatty acid ethylester of the present invention comprises following each step:
(1) pre-treatment:
Crude fish oil adds a certain amount of NaOH aqueous solution, reacts 0.5-3 hour, gets upper strata edible vegetable oil after the centrifugation, wash with water two times, and dehydration, getting stock oil, the standard of stock oil should satisfy:
EPA+DNA ≥25％
Oleaginousness 99%
Iodine number 185
(2) lactideization:
Sodium hydroxide adds ethanol and is made into the sodium hydroxide ethanolic soln, then stock oil is dropped in the there-necked flask, adds the sodium hydroxide ethanolic soln while stirring, and temperature of reaction is 40-60 ℃, and the reaction times is 2-6 hour, gets fatty-acid ethyl ester, i.e. esterised oil; The weight ratio of above-mentioned charging capacity is a stock oil: dehydrated alcohol: sodium hydroxide=1: (0.3-1): (0.01-0.05);
(3) urine bag:
Urea and ethanol are added in the there-necked flask, and stirring and intensification are dissolved urea, add esterised oil then, are warming up to 60-80 ℃, be incubated 5-30 minute, pour reaction solution into large beaker, cooled and filtered is removed and is decrystallized, filtrate water is washed, and tells ethanol liquid, gets polyene fatty acid ethylester (POFA-E); The weight ratio of above-mentioned charging capacity is an esterised oil: ethanol: urea=1: (4-7): (1-2);
(4) rectifying:
The POFA-E that above-mentioned the 3rd step is made adds in the rectifying bottle, is evacuated to the 0.2-0.1 holder, opens water coolant, and the rectifying bottle is warming up to 180 ℃-210 ℃, and product polyene fatty acid ethylester (EPA-E+DHA-E) promptly steams gradually.
The present invention has successfully improved the production technique of original fish oil polyene fatty acid ethylester, through repeatedly experimental results show that, novel process after the improvement is owing to adopted the lactide reaction, shortened the production cycle of former technology widely, reduce raw materials consumption and production cost significantly, improved output and productive rate effectively.Novel process is not only applicable to the extraction of polyene fatty acid and makes with extra care, and the refining of other natural unsaturated fatty acids also had same effect, thereby has considerable economic and obvious social.
Exemplify embodiments of the invention below:
Embodiment 1:
Above-mentioned acceptable material oil 1000 grams are added in the 3000ml there-necked flask, start stirring, be warming up to 50 ℃, add sodium hydroxide ethanol solution (540g dehydrated alcohol+25g solid sodium hydroxide), begin to count the reaction times, reacted 3 hours from adding alkali-ethanolic soln, stopped reaction, reaction solution is moved into separating funnel, washing, standing demix, emit lower floor's water, upper oil phase is washed with water two times, and dehydration gets esterised oil 995g.
Record with the gas-chromatography normalization method:
EPA-E％＝12.81％
DHA-E％＝16.52％
EPA-E+DHA-E％＝29.33％
Ethyl ester transformation efficiency=98.42%
In the urea ethanolic soln that acidity 0.32ml/g has dissolved above-mentioned esterised oil input, be warmed up to 65 ℃, be incubated 30 minutes, pour reaction solution into large beaker while hot, cooling removes by filter crystallization, and filtrate water is washed, tell ethanol liquid, above-mentioned feed ratio is an esterised oil: ethanol: urea=1: 5: 1.The POFA-E that tells gained behind the ethanol liquid is added in the rectifying bottle, give being evacuated to the 0.2-0.1 holder, open water coolant, the rectifying bottle is warming up to 210 ℃, and product steams gradually, when distillation is reached home, closes vacuum valve, emits residue, adds second batch and distills.
Embodiment 2:
Above-mentioned specification stock oil 1000 grams are added in the 3000ml there-necked flask, start stirring, be warming up to 48 ℃, add sodium hydroxide ethanol solution (600g dehydrated alcohol+30g solid NaOH), begin to count the reaction times 2.5 hours reaction times from adding alkali-ethanolic soln, stopped reaction, reaction solution is moved into separating funnel, washing, standing demix, emit lower floor's water, upper oil phase is washed with water two times, and dehydration gets esterised oil 980g.
Record with the gas-chromatography normalization method:
EPA-E％＝12.80％
DHA-E％＝16.54％
EPA-E+DHA-E％＝29.34％
Ethyl ester transformation efficiency=95%
In the urea ethanolic soln that acidity 0.34ml/g has dissolved above-mentioned esterised oil input, be warmed up to 70 ℃, be incubated 20 minutes, pour reaction solution into large beaker while hot, cooling removes by filter crystallization, and filtrate water is washed, tell ethanol liquid, above-mentioned feed ratio is an esterised oil: ethanol: urea=1: 5.5: 1.5.The POFA-E that tells gained behind the ethanol liquid is added in the rectifying bottle, give being evacuated to the 0.2-0.1 holder, open water coolant, the rectifying bottle is warming up to 200 ℃, and product steams gradually, when distillation is reached home, closes vacuum valve, emits residue, adds second batch and distills.
Embodiment 3:
Above-mentioned specification stock oil 1000 grams are added in the 3000ml there-necked flask, start stirring, be warming up to 55 ℃, add NaOH ethanol solution (500g dehydrated alcohol+20g solid NaOH), begin to count the reaction times 4 hours reaction times from adding alkali-ethanolic soln, stopped reaction, reaction solution is moved into separating funnel, washing, standing demix, emit lower floor's water, upper oil phase is washed with water two times, and dehydration gets esterised oil 996.5g.
Record with the gas-chromatography normalization method:
EPA-E％＝12.78％
DHA-E％＝16.32％
EPA-E+DHA-E％＝29.10％
Ethyl ester transformation efficiency=99.54%
In the urea ethanolic soln that acidity 0.30ml/g has dissolved above-mentioned esterised oil input, be warmed up to 75 ℃, be incubated 10 minutes, pour reaction solution into large beaker while hot, cooling removes by filter crystallization, and filtrate water is washed, tell ethanol liquid, above-mentioned feed ratio is an esterised oil: ethanol: urea=1: 6: 2.The POFA-E that tells gained behind the ethanol liquid is added in the rectifying bottle, give being evacuated to the 0.2-0.1 holder, open water coolant, the rectifying bottle is warming up to 190 ℃, and product steams gradually, when distillation is reached home, closes vacuum valve, emits residue, adds second batch and distills.
Claims (1)
1, a kind of new process of production of fish oil polyene fatty acid ethylester is characterized in that this production technique comprises following each step:
(1) pre-treatment:
Crude fish oil adds a certain amount of NaOH aqueous solution, reacts 0.5-3 hour, gets upper strata edible vegetable oil after the centrifugation, wash with water two times, and dehydration, getting stock oil, the standard of stock oil is:
EPA+DNA ≥25％
Oleaginousness 99%
Iodine number 185
(2) lactideization:
Sodium hydroxide adds ethanol and is made into the sodium hydroxide ethanolic soln, then stock oil is dropped in the there-necked flask, adds the sodium hydroxide ethanolic soln while stirring, and temperature of reaction is 40-60 ℃, and the reaction times is 2-6 hour, gets fatty-acid ethyl ester, i.e. esterised oil; The weight ratio of above-mentioned charging capacity is a stock oil: dehydrated alcohol: sodium hydroxide=1: (0.3-1): (0.01-0.05);
(3) urine bag:
Urea and ethanol are added in the there-necked flask, and stirring and intensification are dissolved urea, add esterised oil then, are warming up to 60-80 ℃, be incubated 5-30 minute, pour reaction solution into large beaker, cooled and filtered is removed and is decrystallized, filtrate water is washed, and tells ethanol liquid, gets polyene fatty acid ethylester (POFA-E); The weight ratio of above-mentioned charging capacity is an esterised oil: ethanol: urea=1: (4-7): (1-2);
(4) rectifying:
The POFA-E that above-mentioned the 3rd step is made adds in the rectifying bottle, is evacuated to the 0.2-0.1 holder, opens water coolant, and the rectifying bottle is warming up to 180 ℃-210 ℃, and the product polyene fatty acid ethylester promptly steams gradually.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95118369A CN1056827C (en) | 1995-11-24 | 1995-11-24 | Technique for prodn. of fish oil polyene fatty acid ethylester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95118369A CN1056827C (en) | 1995-11-24 | 1995-11-24 | Technique for prodn. of fish oil polyene fatty acid ethylester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1132195A true CN1132195A (en) | 1996-10-02 |
| CN1056827C CN1056827C (en) | 2000-09-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN95118369A Expired - Fee Related CN1056827C (en) | 1995-11-24 | 1995-11-24 | Technique for prodn. of fish oil polyene fatty acid ethylester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1056827C (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1072711C (en) * | 1998-01-05 | 2001-10-10 | 山东禹王制药有限公司 | Industrial production of highly unsaturated fatty acid |
| CN1084380C (en) * | 1999-08-30 | 2002-05-08 | 朱惠祥 | Process for producing refined fish oil with high polyenoic acid ethyl ester content from crude fish oil |
| CN102911795A (en) * | 2012-11-26 | 2013-02-06 | 天津大学 | Method for preparing fish oil ethyl ester by microwave esterification and purifying ethyl eicosapentaenoate |
| CN102994236A (en) * | 2012-12-11 | 2013-03-27 | 成都圆大生物科技有限公司 | Method for preparing fatty acid ethyl ester with Omega-3 content of more than 90 percent |
| CN103571633A (en) * | 2013-11-15 | 2014-02-12 | 潘见 | Esterification-ultrahigh pressure crystallization separation method for distillate of vegetable oil |
| WO2016058284A1 (en) * | 2014-10-13 | 2016-04-21 | 浙江医药股份有限公司新昌制药厂 | Method for preparing glyceride type polyunsaturated fatty acids |
| CN105779140A (en) * | 2014-12-23 | 2016-07-20 | 浙江医药股份有限公司新昌制药厂 | Preparation method of ethyl ester type fish oil with high EPA content |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3461378B2 (en) * | 1994-04-06 | 2003-10-27 | 日本化学飼料株式会社 | Purification method of eicosapentaenoic acid or its ester |
| JP3576838B2 (en) * | 1998-11-06 | 2004-10-13 | 日本電気株式会社 | Optical disc playback device |
-
1995
- 1995-11-24 CN CN95118369A patent/CN1056827C/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1072711C (en) * | 1998-01-05 | 2001-10-10 | 山东禹王制药有限公司 | Industrial production of highly unsaturated fatty acid |
| CN1084380C (en) * | 1999-08-30 | 2002-05-08 | 朱惠祥 | Process for producing refined fish oil with high polyenoic acid ethyl ester content from crude fish oil |
| CN102911795A (en) * | 2012-11-26 | 2013-02-06 | 天津大学 | Method for preparing fish oil ethyl ester by microwave esterification and purifying ethyl eicosapentaenoate |
| CN102994236A (en) * | 2012-12-11 | 2013-03-27 | 成都圆大生物科技有限公司 | Method for preparing fatty acid ethyl ester with Omega-3 content of more than 90 percent |
| CN102994236B (en) * | 2012-12-11 | 2015-03-25 | 成都圆大生物科技有限公司 | Method for preparing fatty acid ethyl ester with Omega-3 content of more than 90 percent |
| CN103571633A (en) * | 2013-11-15 | 2014-02-12 | 潘见 | Esterification-ultrahigh pressure crystallization separation method for distillate of vegetable oil |
| WO2016058284A1 (en) * | 2014-10-13 | 2016-04-21 | 浙江医药股份有限公司新昌制药厂 | Method for preparing glyceride type polyunsaturated fatty acids |
| US10030212B2 (en) | 2014-10-13 | 2018-07-24 | Zhejiang Medicine Co., Ltd. Xinchang Pharmaceutical Factory | Method for preparing glyceride type polyunsaturated fatty acids |
| CN105779140A (en) * | 2014-12-23 | 2016-07-20 | 浙江医药股份有限公司新昌制药厂 | Preparation method of ethyl ester type fish oil with high EPA content |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1056827C (en) | 2000-09-27 |
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